Cardiovascular disease (CVD), principally heart disease and stroke, is the leading cause of death for both men and women, among all racial and ethnic groups in developed countries. It is also an increasing problem for developing countries. Almost 1 million Americans die of CVD each year, which is approximately 42% of all deaths. Complications of CVD often results in a long?term, severe reduction in quality of life. The limited ability of the damaged heart to heal, and of new blood vessels to grow after myocardial infarction are the main reasons for these long term complications, specifically of heart failure. Our laboratory focuses on the role of stem cells in cardiovascular regeneration. We are isolating rare stem cell populations from the bone marrow of adults. These cells called Multipotent Adult Progenitor Cells (MAPCs) represent a subpopulation of Mesenchymal Stromal Cells (MSC) but have the unique properties of being able to differentiate into almost all tissues of the body. When these MAPCs are injected into a developing mouse embryo, they contribute to all organ structures (except the germ line) properties that make them similar to embryonic stem cells except that they are derived from adults, not embryos. We are investigating the molecular mechanisms that enable MAPCs to differentiate into endothelial and smooth muscle cells, the major cell populations found in normal blood vessel, as well as cardiomyocytes. At present we are testing characterized MAPCs in rat and mouse injury models. We have developed a hind limb ischemia model in rats and are testing and comparing different stem cell types (MAPC, MSC and ES-cell) in their ability to improve not only the perfusion but also the function of ischemic hind limbs. Understanding the function including the molecular and cellular pathways of stem cells is critical to the design and development of new therapies for cardiovascular diseases. We anticipate that by better understanding the biology of these adult stem cells and their role in cardiac regeneration, new therapeutic interventions may be developed to improve the outcome of the many patients that suffer from chronic cardiac diseases.